Recently an outbreak of atypical pneumonia designated severe acute respiratory syndrome (SARS) caused by a coronavirus (SARS-CoV) emerged first in humans in China and then spread to different countries. There is evidence that certain wildlife species are the reservoir for the SARS-CoV. In addition to its high morbidity and mortality rate in humans, this emerging zoonosis also is having a tremendous impact on the global economy. Prophylactic immunization is the most effective solution to control SARS in humans and to eradicate the SARS virus reservoirs in animals. Our preliminary data indicate that SARS virus-specific antibodies can be induced in mice through vaccination with rabies virus (RV) -based recombinant virus vaccines expressing the SARS-CoV S protein. Thus, we propose to develop replication-competent and replication-deficient recombinant SARS-S(N)-RVs that can be used for immunization of animals and humans against SARS, and to identify the immune effectors that contribute to protection against SARS. Because recombinant RVs can replicate in cells of the mucosal membrane, these constructs are uniquely suited to induce the mucosal immunity which might play a major role in the defense against SARS. Results of these experiments will have practical implications for vaccine development, and will provide insight into the factors that stimulate immunity against SARS.